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Sodium hydride → HCID 71280112, compound

HRID 246451
Notes
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Reaction equation

HRID 246451 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:37][C:38]1[CH:42]=[CH:41][O:40][N:39]=1>CN(C=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[CH:18][N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH2:37][C:38]2[CH:42]=[CH:41][O:40][N:39]=2)=[CH:4][CH:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 104646163-(Bromomethyl)-1,2-oxazoleHCID 712803652-(6-chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280112HCID 71280112, compoundYield 97.6%

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-(6-Chloro-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (80 mg, 165 μmol) was dissolved in DMF (1 mL) and cooled to 0° C. Sodium hydride (10.6 mg, 264 μmol) was added and the mixture was stirred for 30 min at 0° C. 3-(Bromomethyl)isoxazole (29.4 mg, 181 μmol) was added and the mixture warmed to room temperature. After 15 h, the mixture was diluted with water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 20-50% ethyl acetate in hexanes, 15 min gradient) gave 2-(6-chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (91 mg, 161 μmol, 97.5%) as a yellow powder. MS (M+Na)+=588 (88% purity); 1H NMR (CDCl3) δ: 9.27 (s, 1H), 8.47 (d, J=8.7 Hz, 1H), 8.34-8.43 (m, 2H), 8.16 (d, J=8.3 Hz, 1H), 8.03 (s, 1H), 7.57 (s, 1H), 6.33 (d, J=1.5 Hz, 1H), 5.77 (s, 2H), 5.73 (s, 2H), 4.38-4.56 (m, 1H), 3.53-3.65 (m, 2H), 1.35-1.46 (m, 6H), 0.89-1.01 (m, 2H), −0.07-0.02 (m, 9H)

Workup

  1. temperaturethe mixture warmed to room temperature
  2. waitAfter 15 h
  3. extractionextracted with ethyl acetate
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (silica, 24 g Analogix column, 20-50% ethyl acetate in hexanes, 15 min gradient)

Sources & evidence

ORD record
ord-9cda683c59b64e22b52a4745d9219696
Source dataset
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08658646B2

Reaction notes

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